DREAMM-7 and DREAMM-8 Data Support Belantamab Mafodotin–Based Combos in R/R Myeloma

Subgroup analyses of outcomes among patients with high-risk features and patient-reported outcomes (PROs) from the phase 3 DREAMM-7 trial (NCT04246047), along with topline findings from the phase 3 DREAMM-8 trial (NCT04484623), further support the use of belantamab mafodotin-blmf (Blenrep) alongside standard-of-care (SOC) regimens in relapsed/refractory multiple myeloma, according to Suzanne Trudel, MSc, MD.^1-3 

“[DREAMM-7 and DREAMM-8] were designed in parallel, but when you put the 2 studies together, [the data] show that belantamab mafodotin performs very well when combined with other anti-myeloma therapies,” Trudel stated in an interview with OncLive^®, adding that “The safety profile is as expected with [these] combinations.”

At the 2024 EHA Congress, findings from the DREAMM-7 trial showed that the combination of belantamab mafodotin, bortezomib (Velcade), and dexamethasone (BVd) maintained a progression-free survival (PFS) benefit vs daratumumab (Darzalex), bortezomib and dexamethasone (DVd) in both high-risk patients and those refractory to lenalidomide.¹ Additionally, a subsequent analysis of PROs from the clinical trial demonstrated that overall quality of life (QOL), role functioning, physical functioning, fatigue, and pain were comparable among patients treated with BVd vs DVd.²

Additionally, data from the DREAMM-8 trial evaluating belantamab mafodotin plus pomalidomide (Pomalyst) and dexamethasone (BPd) vs bortezomib plus pomalidomide and dexamethasone (PVd), were presented at the 2024 ASCO Annual Meeting. The median PFS was not reached (NR; 95% CI, 20.6 months to NR) with BPd and was 12.7 months (95% CI, 9.1-18.5) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P <.001). Moreover, the risk of disease progression or death was reduced with the BPd regimen in difficult-to-treat patient subgroups, including those with cytogenic or functional high-risk disease, refractory disease following lenalidomide (Revlimid), and prior treatment with anti-CD38 therapy.³

In the interview, Trudel detailed updated data from the DREAMM-7 and DREAMM-8 studies, discussed the impact of these data on the treatment of patients with relapsed/refractory multiple myeloma, and emphasized the robust efficacy of these respective treatment regimens.

Trudel serves as an associate professor at the University of Toronto and is a clinician scientist Princess Margaret Cancer Centre, in Canada.

OncLive: What previous data reported from DREAMM-7 helped inform the design of DREAMM-8?

The efficacy [of adding belantamab mafodotin to standard regimens] is significant when compared with the control arm in both DREAMM-7 and DREAMM-8. [These data] speak to the robustness of belantamab mafodotin in combination as well as the use of these agents in earlier lines of therapy.

What was the rationale for investigating the addition of belantamab madodotin to standard Pd in relapsed/refractory multiple myeloma?

The rationale for [adding belantamab mafodotin to] the combination of pomalidomide and dexamethasone in DREAMM-8 was based on preclinical work that showed synergy with immunomodulatory drugs. We also know that immunomodulatory drugs, in general, combine well with monoclonal antibodies; they tend to synergize that activity. That was supported by clinical data with other monoclonal antibodies.

Additionally, [the rationale for this research was supported by] the [phase 1/2] ALGONQUIN study [NCT03715478], which was a pan-Canadian trial that explored the combination pomalidomide and dexamethasone and showed quite robust efficacy data, and safety as well.

What treatment approaches were evaluated in DREAMM-8?

The study was designed to address an unmet need in our current population of patients who are progressing after 1 prior line of therapy. We knew that the area was evolving with more and more patients being exposed [to lenalidomide], and many being refractory to lenalidomide. Based on this need, that was one of the inclusion criteria, that patients had to have prior lenalidomide exposure.

In trying to determine what the control arm would be, we wanted to also capture patients who would be anti-CD38 exposed, hence why we chose a non–anti-CD38 comparator arm to allow for the enrollment of that patient population, knowing that anti-CD38 agents were moving into the upfront setting.

What efficacy data from the analysis were presented at the 2024 ASCO Annual Meeting?

The results showed that the study met its primary end point of PFS, with a clinically meaningful and statistically significant reduction in risk of death of progression by 48%. All the efficacy end points favored the combination arms, including depth and durability response. There was also an important trend towards improvement in OS, with a HR of 0.77. This data showed robust efficacy for all end points.

What should be known about the safety profile of BPd?

The safety profile was consistent with the individual agents we used in the combination. The most commonly reported adverse effects [AEs] were neutropenia, thrombocytopenia, and infection, as well as ocular toxicities. The ocular events that we saw are consistent with what we would expect with an MMAF-containing antibody-drug conjugate, which was what belantamab mafodotin is. These were commonly reported, but overall were reversible in most patients.

How might these findings impact clinical practice, and what next steps are planned for this research?

These belantamab mafodotin combinations represent a new potential SOC for patients in early relapse. We know that there's a clinical gap in that patient population now, with the use of lenalidomide and anti-CD38’s in the front line. Outcomes with our currently available therapies are not great, so this provides an option for patients in that scenario.

It also provides clinicians with the opportunity to have access to a drug that's off the shelf, can be given in a community setting with a very manageable safety profile.

What key data from subgroup analyses of DREAMM-7 were presented at the 2042 EHA Congress?

DREAMM-7 was a phase 3 study that combined belantamab mafodotin with bortezomib and dexamethasone and compared it with DVd, showing a significant improvement in PFS, as well as an important trend to OS in that study as well.

At the 2024 EHA Congress, investigators presented some of the subgroup analyses, and importantly, they're showing data in patients that are lenalidomide-refractory, which was approximately a third of the patients that were enrolled onto the study. This data showed that the median PFS [with BVd] is 25 months, superior to outcomes in lenalidomide-refractory disease with SOC therapies.

Data was also shared for high-risk patients, as they are particularly difficult-to-treat patient population. That data are quite fascinating, because the PFS for the high-risk patients is consistent with what was seen in the intention-to-treat population; we haven't really seen that in any other studies.

Usually there's always an improvement in PFS in high-risk patients, but it usually doesn't equal that of the intention-to-treat population. I think this is an important finding.

What is the importance of learning more about PROs with BVd in this patient population?

PROs [are important] because there's a lot of concern around ocular toxicities and how that may impact patients. We know this may affect their ability to drive, to read, or watch television, but I think overall, the QOL assessments and PROs were stable throughout the time of treatment. This suggests that BVd doesn't negatively impact patients' day-to-day lives.

References

1. Mateos MV, Robak P, Hus M, et al. DREAMM-7 update: Subgroup analyses from a phase 3 trial of belantamab mafodotin + bortezomib and dexamethasone vs daratumumab, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Presented at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract P938.
2. Hungria V, Robak P, Hus M, et al. Patient-reported outcomes from DREAMM-7 a randomized phase 3 study of belantamab mafodotin, bortezomib + dexamethasone (dex) vs daratumumab, bortezomib + dex in relapsed/refractory multiple myeloma. Presented at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract P945.
3. Trudel S, Beksac M, Pour L, et al. Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;(suppl 17):LBA105.